The asymmetric reaction catalyzed by chiral transition metal complexes is the most effective method to obtain optically active chiral compounds, and has been widely used in the industrial production of chiral drugs. In asymmetric catalytic reaction, High-efficiency and high-selectivity results can be realized for synthesizing chiral compounds with the key chiral ligands or catalysts to be used. For this reason, in the past decades of researching, the development of new high-efficiency and high-selectivity chiral ligands and their catalysts has always been of concern.
As far as now, for ligands which were used very common and frequency in asymmetric catalytic hydrogenation reactions in industrial production, so far there have been thousands of chiral ligands and their catalysts reported in the literature, however, with little successful results come out. So the catalysts both with high catalytic activity (the TON value is up to 100,000) and high enantioselectivity (the ee value >99%) are still few and scarce (Zhou, Q.-L. Eds, Privileged Chiral Ligands and Catalysis, Wiley-VCH: 2011; Caprio, V.; Williams, J. M. J., Eds, Catalysis in Asymmetric Synthesis; Wiley-VCH: Chichester, 2009; de Vries, J. G.; Elsevier, C. J. Eds.; The Handbook of Homogeneous Hydrogenation; Wiley-VCH: Weinheim, 2007). Recently, our research group has designed and synthesized a kind of chiral spiro-pyridylamidophosphine tridentate ligand Spiro PAP with novelty structure (Xie, J.-H.; Liu, X.-Y.; Xie, J.-B.; Wang, L.-X.; Zhou, Q.-L. Angew. Chem. Int. Ed. 2011, 50, 7329-9332. Zhou Qilin, Xie Jianhua, Liu Xiaoyan, Xie Jianbo, Wang Lixin CN102040625A), its iridium complex Ir-Spiro PAP has a very prominent performance in the asymmetric catalytic hydrogenation reaction of carbonyl compounds, and the enantioselectivity value can be up to 99% ee, the TON value can be up to 4.50 million. The iridium catalyst Ir-Spiro PAP of the chiral spiro-pyridylamidophosphine tridentate ligand is also very effective for the asymmetric catalytic hydrogenation reaction of β-keto esters with the enantioselectivity value up to 99% ee and the TON value can be up to 1.23 million (Xie, J.-H.; Liu, X.-Y.; Yang, X.-H.; Xie, J.-B.; Wang, L.-X.; Zhou, Q.-L. Angew. Chem. Int. Ed. 2012, 51, 201-203). However, the chiral spiro iridium catalyst Ir-Spiro PAP only has a high enantioselectivity for β-aryl-β-keto ester, it just has a moderate enantioselectivity for β-alkyl-β-keto ester (<60% ee).
At present, the catalyst which has high-performance in asymmetric catalytic hydrogenation of β-alkyl-β-keto ester is limited to the ruthenium halide catalyst of chiral diphosphonic ligand, but the TON value of the most catalysts are not beyond ten thousand. And they were often required to add hydrochloric acid and other additives, which are corrode to metal reactors (Ohkuma, T.; Noyori, R. in Handbook of Homogeneous Hydrogenation, Eds.: de Vries, J. G.; Elsevier, C. J., Wiley-VCH, Weinheim, 2007, pp. 1105).
Therefore, Considering the importance application of asymmetric catalytic hydrogenation reaction of β-alkyl-β-keto ester in synthesizing chiral drugs, designing and developing novelty high-efficiency chiral ligands and catalysts can still be very significant although full of difficulty and challenge.